As a method of administering a drug to a human body, oral administration and transdermal administration are often used. Injection is a typical transdermal administration method. However, injection is a procedure which takes time and labor of specialists such as physicians and nurses, is painful and is likely to cause an infection of AIDS, hepatitis B etc. so that many people do not welcome the procedure. In contrast, a transdermal administration method without pain using a microneedle array has been recently attracting attention (Non-patent Document 1).
In transdermal administration of a drug, stratum corneum works as a barrier to drug permeation so that only applying a drug on a skin surface cannot cause enough permeability. In contrast, perforation of corneum by using a minute needle, i.e. a microneedle can remarkably improve efficiency in drug administration compared to that in the application method. It is a microneedle array in which a large number of the microneedles are integrated on a substrate. In addition, a product in which various tapes such as an adhesive tape for adhering the microneedle array to a skin and a cover sheet for maintaining an aseptic state until its use are added to the microneedle array in order to facilitate its use is called a microneedle patch.
Herein, a tape means a film to which an adhesive agent is applied.
Initially, metals and silicon had been used as base materials for the microneedle. A method in which a skin is perforated by stainless-steel needles and a drug solution is casted so that the pores absorb the drug (Patent Document 1), and a method in which surfaces of a stainless-steel needles are coated with a drug and then the needles are inserted to administer the drug (Patent Document 2) were proposed. Furthermore, it was also proposed that a drug solution is injected by hollow microneedles made by simply micronizing injection needles (Patent Document 3).
However, there were some drawbacks as followings: the drug solution-casting method not only had low efficiency of drug incorporation but also its sterility was doubtful; in the coating method, the efficiency of drug incorporation became low due to removal of the coating drug during insertion; and in the micronized injection needle method, the structure was complicated. Furthermore, when the microneedles made of metals or silicon broke in a body, it might cause an accident and this is a drawback.
In contrast, if the microneedles are prepared with a substance which dissolves in a body, such problems can be solved (Patent Document 4). In addition, if a polymer which dissolves by moisture in a skin after transdermal administration (i.e. biosoluble polymer) is used as a material for the microneedles, the application of the microneedles to the skin allows the skin moisture to diffuse into the needles, and the needles inserted into the skin swell and then dissolve. The dissolution of the needles causes diffusion of hyaluronic acid or collagen in the skin which express an anti-wrinkle effect, or dispersion in the skin of a drug or a valuable substance previously dissolved in the needles (Patent Documents 5 and 6).
A microneedle array made of the biosoluble polymer is often manufactured by using a mold (Patent Document 5). A microneedle pattern is formed by lithography using a photosensitive resin, and then transferred for preparing a mold having concave portions for forming the microneedles. A base material of the microneedles is casted onto this mold, subsequently heated to vaporize moisture, and then the solidified material is removed from the mold to obtain the microneedle array.
Some drugs to be contained in the microneedle array are extremely expensive, or can be obtained only in minute amounts. When such an expensive and valuable drug is contained in a base material to prepare a microneedle array by a conventional method, the drug would be contained not only in the microneedle portion but also in its substrate portion (Patent Document 7). When this microneedle array is inserted into a skin, a drug contained in the microneedle portion is incorporated and diffused in a body, but the drug remaining in the substrate portion is discarded without utilization, resulting in low usage efficiency of the valuable drug.
Some trials for efficient utilization of valuable drugs are already known. In addition to the method in which the surfaces of the microneedles are coated (Patent Document 2), a method in which a drug is applied to tips of microneedles (Patent Document 8), a method in which a drug is converged to tips of needles by centrifugation while the microneedles maintain softness (Patent Document 9), and a method in which a mold is filled with a solution of a drug-containing base material, dried, and then filled with a solution of base material without drug so as to hold the drug only in tips of the microneedles (Patent Document 10), etc have been reported. The method of Patent Document 8 in which this drug is applied to the tips is characterized in that the drug is dissolved by heating it to about 100° C. and applied to the tips of the microneedles.